Bhujel Basanta, Oh Se-Heon, Hur Woojune, Lee Seorin, Lee Hun, Chung Ho-Seok, Kim Jae Yong
Department of Ophthalmology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
Department of Medical Science, University of Ulsan Graduate School, Seoul 05505, Republic of Korea.
Int J Mol Sci. 2025 Apr 21;26(8):3922. doi: 10.3390/ijms26083922.
Particulate matter (PM) exposure is known to induce significant ocular surface inflammation, necessitating effective therapeutic interventions. This study compared the efficacy of 2% rebamipide (REB) with 0.1% hyaluronic acid (HA) eye drops in investigating the anti-inflammatory and pathogen-clearance effects in a PM-induced ocular surface inflammation model using Sprague-Dawley (SD) rats. Parameters including clinical signs, histological changes, mucin secretions, inflammatory cytokines, mast cell degranulation, dysregulated cell proliferation, and cellular apoptosis were evaluated. 2% REB alleviated ocular surface inflammation by downregulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory pathway and upregulating epidermal growth factor receptor (EGFR) signaling, thereby enhancing mucin secretion and promoting pathogen clearance. Histopathological analysis, western blot, and immunohistochemical staining revealed a marked reduction in inflammatory markers including MMP-9, IL-1β, TNF-α, IL-17, and CD-4, decreased mast cell degranulation, increased goblet cell density, and enhanced expression of mucins, including MUC5AC and MUC16, in the 2% REB-treated group compared to the 0.1% HA-treated and PM-exposed groups. Moreover, 2% REB demonstrated decreased apoptosis (TUNEL) and reduced uncontrolled cell proliferation (Ki67), indicating improved cellular integrity. In conclusion, 2% REB is a promising treatment option for PM-induced ocular surface inflammation in a rat model compared with 0.1% HA, offering the benefits of reducing inflammation, clearing pathogens, and protecting overall ocular health.
已知接触颗粒物（PM）会引发显著的眼表炎症，因此需要有效的治疗干预措施。本研究比较了2%瑞巴派特（REB）与0.1%透明质酸（HA）滴眼液在Sprague-Dawley（SD）大鼠PM诱导的眼表炎症模型中的抗炎和病原体清除效果。评估了包括临床体征、组织学变化、粘蛋白分泌、炎性细胞因子、肥大细胞脱颗粒、细胞增殖失调和细胞凋亡等参数。2%瑞巴派特通过下调活化B细胞核因子κB（NF-κB）炎症通路和上调表皮生长因子受体（EGFR）信号传导来减轻眼表炎症，从而增强粘蛋白分泌并促进病原体清除。组织病理学分析、蛋白质免疫印迹和免疫组织化学染色显示，与0.1%透明质酸治疗组和PM暴露组相比，2%瑞巴派特治疗组的炎性标志物包括基质金属蛋白酶-9（MMP-9）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-17（IL-17）和CD-4显著减少，肥大细胞脱颗粒减少，杯状细胞密度增加，粘蛋白包括MUC5AC和MUC16的表达增强。此外，2%瑞巴派特显示细胞凋亡（TUNEL）减少，细胞增殖失控（Ki67）降低，表明细胞完整性得到改善。总之，与0.1%透明质酸相比，2%瑞巴派特是大鼠模型中PM诱导的眼表炎症的一种有前景的治疗选择，具有减轻炎症、清除病原体和保护整体眼部健康的益处。
